1. Field of the Invention
The present invention relates to a microchip valid for a μ-TAS(Micro Total Analysis System) and the like, suitable for use in environmental analysis, chemical synthesis and biochemical assays of DNA, protein, cells, immunity, blood and the like.
2. Description of the Background Art
In line with the recent increase in the importance of sensing, detecting and determining the quantity of chemical substances and biological material such as DNA (Deoxyribo Nucleic Acid), enzyme, antigen, antibody, protein, virus, and cells in the field of medical care, health, food product, development of medicine and the like, various biochips and microchemical chips (hereinafter, generically referred to as a microchip) that allow relevant measurement conveniently have been proposed (for example, Japanese Patent Laying-Open No. 2007-017342). A microchip is characterized in that the series of experiments and analytical operations carried out at laboratories can be performed within a chip that is several to 10 cm square and several millimeters to several centimeters in thickness. Accordingly, only a small amount of specimen and reagent is required, leading to reduction in cost. Assays can be performed with a high response rate and high throughput. Another advantage is that the examination result can be obtained immediately at the site where the specimen has been collected. A microchip can be used conveniently in biochemical examination such as a blood test.
A microchip has fluid circuits therein. The fluid circuits are mainly constituted of a plurality of sites such as a liquid reagent receptacle unit to store a liquid reagent directed to mixing or reacting with, or treating a specimen (for example, blood), a quantification unit to quantify a specimen and/or liquid reagent, a mixing unit to mix the specimen and liquid reagent, and a cuvette (detection unit) for optical measurement to examine and/or analyze the mixture, as well as minute channels appropriately connecting the sites. In use, a microchip is typically mounted on an apparatus (a centrifuge) that can apply centrifugal force to the chip. By applying centrifugal force to the microchip in an appropriate direction, measurement and mixture of a specimen and/or liquid reagent, in addition to introduction of the mixture to the optical measurement cuvette, can be effected. The examination and analysis of the mixture introduced into the optical measurement cuvette (for example, detection of a certain component in the mixture) can be implemented by directing light to the cuvette in which the mixture is stored and measure the transmissivity or the like.
In the examination and/or analysis based on the above-described microchip, a guarantee that the liquid treatment in the fluid circuits effected by application of centrifugal force is extremely critical. This is because, if such guarantee cannot be afforded, evaluation as to whether the result of the examination and analysis is reliable or not cannot be made. Unreliable situations include, for example, the case where the liquid reagent that should be stored in the liquid reagent receptacle unit at the time of using the microchip is not present at a predetermined location or is insufficient due to evaporation or drop off during transportation, the case where the introduced amount of specimen into the fluid circuits is insufficient, and the case where liquid leakage has occurred due to a defect in the fabrication of the microchip. In such cases, the quantified amount of liquid reagent and specimen will not be accurate, leading to incorrect resultant data from the examination and analysis. There is also the possibility of erroneous operation at the centrifuge equipment, which may impede appropriate fluid transfer. Therefore, a guarantee that the fluid in the fluid circuits is transferred to an appropriate site, fluid treatment is carried out appropriately, the amount of the specimen and/or liquid reagent is sufficient, without erroneous operation of the centrifuge equipment, is critical. However, the approach to actually introducing a specimen into the fluid circuits to conduct fluid treatment, and checking whether there is the aforementioned error, prior to the examination and analysis based on a microchip (actual usage), cannot be employed since a microchip is generally not reusable.
U.S. Pat. No. 5,590,052 discloses a method for confirming that the fluid introduced into a blood analysis system has flown to a predetermined site. This method includes the steps of directing light to a predetermined site, and detecting the passing light.
The microchip disclosed in the aforementioned Japanese Patent Laying-Open No. 2007-017342 is formed by uniting together a first substrate with grooves that correspond to fluid circuits, and a second substrate. The first and second substrates are united such that the surface of the first substrate where grooves are provided corresponds to the joining face. The microchip includes one layer of fluid circuits therein. As used herein, “one layer” implies that the microchip includes only one fluid circuit layer in the thickness direction of the microchip.
In a microchip directed to a blood test, various types of examinations are often performed using the blood plasma component in the whole blood. Therefore, fluid circuits in such a microchip generally includes a blood plasma separator unit to remove hematocytes from the whole blood introduced into the fluid circuits to extract and separate the plasma component.